Process for introducing delta unsaturation into steroids



. 3,023,205 PROCESS FOR INTRODUCING A UNSATURATION INTO STEROIDS Derek Burn, David Neville Kirk, Vladimir Petrow, and

George Oliver Weston, all of London, England, assignors to The British Drug Houses Limited, London, England, a British company No Drawing. Filed Mar. 11, 1-959, Ser. No. 798,609

Claims priority, application Great Britain Mar. 13, 1958 12 Ciaims. (Cl. 260-239.55)

This invention is for improvements in or relating to organic compounds and has particular reference to the l-dehydro derivatives of certain unsaturated steroidal 3- ketones.

Steroids possessing the B-oXo-A and 3-oxo-A systems are of particular value on account of their biological properties which are often considerably enhanced in relation to those of the corresponding. 3-oxo-A and 3-oxo-M analogues.

Such l-dehydro steroids have been previously prepared by one of the following procedures.

The corresponding 3-oxo-A -steroid may be oxidised with selenium dioxide, or it may be converted into a halo genated derivative which is then dehydrohalogenated to yield the required l-dehydro analogue. These processes are in general unsatisfactory due to the difficulty' in carrying out the reactions and the low yields obtainable. In addition, l-dehydro steroids may also be prepared by microbiological dehydrogenation of a suitable precursor,

which process is however expensive to carry out and re-,

quires specialised equipment and techniques.

' We have now found that 3-ox0-A and 3-oxo-A steroids may be converted in excellent yields into the corresponding l-dehydro analogues by a simple, one-stage chemical process.

a United States Patent.

nitrobenzene, acetic acid or propyl acetate. The dehydrogenationreaction is preferably carried out at an ele- It is also an object of the invention to provide certain 7 new l-dehydro steroids which are of value on account of their biological: properties or as intermediates in the preparation of compounds having useful biological propc ties as is apparent to those skilled in the art.

According to the present invention there is provided a process for the preparation of 3-oxoand 3-oxo-A steroids having the formula (with or without a double bond at the 6:7 position) which process comprises treating the corresponding 3- oxo-A or 3-oxo-A -steroids having the formula (with or without a doublebond at. the 6:7 position) with 2: 3-dicyano-l :4-benzoquinone, which may be additionally substituted with one or two chlorine atoms, in a solvent.

Preferably 2:3 dicyano 5:6 dichloro 1:4 -.benzoquinone is employed. (See J.C.S., 1954, 3569, for the preparation of these two quinones.)

The solvent may be benzene, dioxan, dimethylene glycol dimethyl ether, chlorobenzene, dimethylformamide,

vated temperature and conveniently between 80 C. and

110 C. Theoretically the reaction is best performed in an inert atmosphere such asfor example nitrogen, but this precaution has little practical significance in the majority of cases herein. The rate of reaction may be increased by the addition of a catalytic amount of a proton donor, and in particular by the addition of a catalytic amount of p-nitrophenol. Completion of the reaction is generally indicated by the discharge of the colourv of the quinone and/ or by the fact that further quantities of 2:3-dicyano-5 :6-dichloro-1 :4 dihydroxy benzene arev no longer deposited from the hot reaction liquors. ternatively, completion of the reaction may be determined by estimating the quantity of the quinone present in the reaction liquors by standard methods well known to those skilled in the art.

The l-denydro steroid derivative is isolated from the reaction liquor by any convenient procedure. Thus the reaction liquors may be filtered to remove the sparingly soluble hydroquinone, extracted with aqueous alkali to remove phenolic products, evaporated to dryness, under reduced pressure if desired, and the residual solids crystallised in the usual way. Other methods will be apparent,

to those skilled in the art.

The process of the invention is of wide applicability and may, in general, be applied to 3-oxo-A and 3-oxo A derivatives of androstane, pregnane, stigmastane, cholestane and spirostane containing additional substituents which do not interfere with the process of the invention as hereinunder indicated.

Oxo groups, and in particular oxo groups in positions C11, 17 and 20 (including 20-oxo-16-ene).

Hydroxy, alkoxy and acyloxy groups, and in particular hydroxy, alkoxy and acyloxy groups in positions C-6, 11, 16 17, 20 and 21.

Fluoro groups, and in particular fiuoro groups in posivatives possessing useful biological properties.

. Thus the 1:4:6 trienes can be converted into aromatic steroids by reaction insolution in acetic anhydride with toluene p -sulphonic acid. While 9a-fiuoro-1 lfizl7B-dihydroxy-17a-methylandrosta-1:4-dien-3-one is the l-dehydro analogue of a known anabolic and androgenic agent and itself has those properties. I

17a-ethynyl-17/3-hydroxyandrosta-l :4: 6-trien-3 -one 17,8-hydroxy-l 7e-methylandrosta-1 :4: 6-trien-3-one Pregna-l :4: 6-triene-3 :20-di0ne l le-hydroxyprcgna-l :4-diene-3 20-dione Pregna-l :4-diene-3 11 :20-trione Pregna-l :4: 6-triene-3 :11 20-trion'e Pregna-l :4: 16-triene-3 :20-dione loot-methyl pregna-l :4-diene+3 :ZO-dione 9a fluoro 11,8 17fl-dihydroxy-l7a-methylandrosta-1:4-

dien-3-one Ethyl 3-oxopregna-1 :4: 17 (20 -trien-2 l-oate 20:20-ethylenedioxypregna-1 z4-dien-3-one 1 Cholesta-l 4-diene-3 G-dione I e Patented Feb-27, 19s;

3 Acetonide of 16a! 17a dihydroxypregna-l :4-diene-3 :20-

dione 175-acetoxy-Z-methylandrosta-1 :4-dien-3-one Pregna-l :4: 9 1 1 -triene-3 20-dione -Following is a description by way of example of methods of carrying the invention into efiect.

EXAMPLE 1 17a-Hydr0xypregn-1 :4-Diene-3z20-Di0ne A solution of17e-hydroxyprogesterone (0.25 g.), 2:3-

dicyano-S:6-dichlorobenzoquinone (0.25 g.) and p-nitro- 2l-Acetoxypregn-1 :4-Diene-3:20-Dione A solution of 21-ace'toxypregn-4-ene-3:20-dione (0.25 g.), 2:3-dicyano-5:G-dichlorobenzoquinone (0.25 g.) and p-nitrophenol (0.05 g.) in dry benzene (5 ml.) was heated under reflux for 5- /2 hours. The product was isolated as described in Example 1 and crystallised from aqueous methanol to give 21-acetoxypregn-1:4-diene-3z20-dione as needles, M.P.204 to 207 C., [a] +137 (c. 0.82 in choloroform), x 244 mmlog e 4.20.

EXAMPLE 3 Pregn-l :4-Diene-3 :20-Di0ne A solution of progesterone (0.2 g.), 2:3-dicyano-5z6- dichlorobenzoquinone (0.2 g.) and, p-nitrophenol (0.02 g.) in dry benzene. (5 ml.) was heated under reflux for 9 hours. The product was isolated as in Example 1 and. crystallised from ether/hexane to give pregn-lz4-diene- 3:20-dione as prisms, M.P. 151 to 153 C., [a] +125 (.c. 0.6 in chloroform), A 244.5 m log 6 4.21.

EXAMPLE 4 21-Acet0xy-1 7a-Hydroxypregn-1 :4-Diene-3:1 1 :20- T rione A solution of cortisone acetate (0.15 g.), 2:3-dicyano- 5,:6-dichlorobenzoquinone (0.15 g.) and p-nitrophenol (0.04 g.) in dry benzene (40 ml.) was heated under refiux for 37 hours. The product was isolated as in Example 1 and crystallised from acetone/hexane to give'21- acetoxy 17oz hydroxypregn-l:4-diener3:11:20 trione as prisms, M.P. 227 to 230 C., [ch -+182 (c. 0.4 in dioxan), )Ynjax 238 m log e 4.19. r

EXAMPLE 5' 25D-Spirosta-1- :4-Dien-3-0ne A solution of diosgenone (0.25" g.) (Marker, Tsukamoto and Turner, J.A.C.S., 1940, 62, 2525), 2:3-dicyano- 5:6-dichlorobenzoquinone (0.25 g.) and p-nitrophenol (0.05 g.) in dry benzene (5 ml.) was heated under refiux for 15 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give25D- spirosta-1:4-dien-3-one as needles, M.P. 192 to 194 C., [A -71 (c. 0.64 in chloroform), A 244.5-m ,.log; e 4.18.

EXAMPLE 6 1713-Prpi0n0xyandr0sta-1 :4-Dien-3-one A solution of testosterone propionate (0.5 g.) and 2:3- dicyauo-S:-dichlorobenzoquinone (0.4 g.), in dry hen.- zene ml.) was heated under reflux for 5% hours.

The product was isolated as in Example 1 and crystallised from acetone/hexane to give 17[3-propionoxyandrosta- 1:4-dien-3-one as laths, M.P. 144 to 146 C., [a] +33 (c. 0.65 in chloroform), A 244 m log 15 4.20.

EXAMPLE 7 1 7 8-Hydroxyana'rosta-l 4-Dien-3-one A solution of testosterone (0.25 g.) and 2:3-dycyano- 5:6-dichlorobenzoquinone (0.25 g.) in dry benzene (5 ml.) was heated under reflux for 15 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give 17B-hydroxyandrosta-1:4-dien-3 one as needles, M.P. 167 to 169 C., [a] -+22 (c. 0.72 in chloroform), A 244.5. m log 6 4.18.

EXAMPLE 8 17fl-Hydr0xy-17a 1'v1'ethylandr0sta-1 :4-Dien-3-0ne 'A solution of 17B-hydroxy-17a methylandrost-4-en-3- one (0.25 g.), 2:3 dicyanO-S':6-dichlorobenzoquinone (0.25 g.) and p-nitrophenol (0.05 g.) in dry benzene (5 ml.) was heated under reflux for 4 hours. The product was isolated as in Example 1 and crystallised from aqueous acetone to give 17&hydroxy-17a-methyl-androsta- 1:4-dien-3-one as needles, M.P. 162 to 164 C., [a] -{-3. (c. 0.65 in chloroform), 1 244.5 III/1., log 6 4.19.

EXAMPLE 9 Androsl-1'24-Diene-3:ZO-Dione A solution of androst-4-ene-3z17-dione (0.25 g.), 2:3- dicyano-S:6-dichlorobenzoquinone (0.25 g.) and p-nitrophenol (0.05 g.) in dry benzene (5 ml.) was heated under reflux for 5 hours. The product was isolated as in Example 1 and crystallised from aqueous acetone to give androsta-l:4-diene-3z20-dione as needles, M.P. 137 to 139 C., [a] +117 (c. 0.42 in chloroform), h 244.5 m log .6 4.22.

EXAMPLE 10 Cholest-I :4-Dien-3-0ne A solution of cholest-4-en-3-one (0.5 g.), 2:3-di'cyano- 5:6-dichlorobenzoquinone- (0.5 g.) and p-nit'rophenol (0.1 g.) in dry benzene (10 ml.) was heated under reflux for 28 hours. The product was isolated-as in Example 1 and crystallised from ethanol to give cholesta-1z4-dien-3- one as prisms, M.P. 111 to 113 C., [a] +27 (c. 0.65 in chloroform), k 244 m log e 4.20.

EXAMPLE 11 Cholesza-I :4 :6-Trien-3-0ne A solution of chol'estae4z6 dien-3-one (0.5 g.) (Wilds and Djerassi, J.A.C.S., 1946, 68, 1712), 2:3-dicyano-5z6- dichlorobenzoquinone (0.5? g.) and p'-nitrophenol (0.1 g.) in dry benzene (10 ml.) was heated under reflux for 7 hours. The product was isolated as in Example 1 and crystallised from ethanol to give cholesta-lz4z6-trieu-3- one as prisms, M.P. 83 to 84 C., [a] +1 (c. 0.42

in chloroform), A 224 m (log 2 4.06), 256 m (log e 4.01) and 300 my (log a 4.07).

EXAMPLE 12 1 1 "H ydroxy pregna-I :4 -Diene-3 20-Di0ne EXAMPLE 13 Pregna-I :4-Diene-3z11 :ZO-Trione A; solution'of pregn'-4-ene-3";llzzfl-trione (1 g.), 2:3-

dicyano-S:6-dichlorobenzoquinone (1 g.) and p-nitrophenol (0.1 g.) in dry benzene (20 ml.) was heated under reflux for 7 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give pregna-1:4-diene-3:11:20-trione as needles, M.P. 167 to 169 C., [u] +249 (c. 0.9 in chloroform), A 238.5 m log 5 4.12, 11 1702, 1661, 1620, 1602 cmr' EXAMPLE 14 1 7 3-Hydr0xyandrosta-1 4 6-Trien-3-an A solution of l7fi-hydroxyandrosta-4:6-dien-3-one (0.53 g.) (Inhofien and Zuehlsdorlf, Ber., 1943, 76, 233'), 2:3-dicyano-5:6-dichlorobenzoquinone (0.5 g.) and pnitrophenol (0.05 g.) in dry benzene ml.) was heated under reflux for 7 /2 hours. The product was isolated as in Example 1 and crystallised from aqueous acetone to give 17,8-hydroxyandrosta-l:4z6-trien-3-one as needles, M.P. 155 to 156 C., [a] +l6.5 (c. 0.32 in chloroform, A 224 m (log e 4.15), 257 mp. (log e 4.17) and 298 m (log 54.16).

EXAMPLE 25D-Spir0sta-I :4 6 -Trien-3-orze A solution of,25D-spirosta-4:6-dien-3-one (0.56 g.) (Marker and Turner, J.A.C.S., 1941, 63, 767) and 2:3- dicyano-5:6-dichlorobenzoquinone (0.55 g.) in dry benzene (10 ml.) was heated under reflux for 10 hours. The product was isolated as in Example 1 and crystallised from dichloromethane/methanol to give ZSD-spirosta- 1:4:6-trien-3-one'as needles, M.P. 209 to 211 C., [oz] -101 (c. 0.29 in chloroform), A 223 my (log 5 4.10), 255 m (log 6 4.07) and 299 m (log 6 4.13).

EXAMPLE l6 Pregna-I :4 :6-Triene-3 :ZO-Dione EXAMPLE 17 17p-Hydr0xy-1 7a-Methylandrosta-1 4 6-Trien-3-0ne A solution of 17B-hydroxy-17a-methylandrosta-4:6- dien-3-one (1 g.) and 2:3-dicyano-5:6-dichlorobenzoquinone (l g.) in dry benzene ml.) was heated under reflux for 12 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give 17/3-hydroxy 17cc methylandrosta 1:4:6 trien-3-one as laths, M.P. 139 to 140 C., [a] -19.l5 (c. 1.0 chloroform), A 223 mp (log 5 4.05), 256.5 my. (log 6 3.96) and 299 my (log t! 4.11).

EXAMPLE 18 Pregna-I :4 :6-Triene-3 1 1 :20-Tri0ne A solution of pregna-4:6-diene-3:11:20-trione (1 g.) (prepared from pregn-4-ene-3,11,20-trione by reaction with chloranil in the manner well-known to the art) and 2:3-dicyano-5:6-dichlorobenzoquinone (l g.) in dry benzene (20 ml.) was heated underrefiux for 14 /2 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give pregna-1:4:6-triene-- 3:11:20-trione as needles, M.P. 177 to 179 C., [a] -|-350.l (c. 1.05 in chloroform), Amax, 225mg.

(log 6 4.01), 254.5 m (log a 3.98) and 296 m z (log 6 EXAMPLE 19 :1 7az21-Trihydrqxypregna-1 :4-D iene-3 20-Di0ne A solution of 1113:l7a:21-trihydroxypregn-4-ene-3:20-

dione (0.5 g.) and 2:3-dicyano-5:6-dich1orobenzoquinone (0.5 g.) in purified dioxan (6 ml.) was heated under reflux for 5 hours. The product was isolated as in Example 1 and crystallised from acetone/hexane to give 11,8:l7az2l-trihydroxypregna-l:4-diene-3:20-dione as a micro-crystalline powder,- M.P. 236 to 240 C., [a] -l-100 (c. 0.22 in dioxan), A 244 my, log e 4.15. I

EXAMPLE 20 17e-Ethynyl-17p-Hydroxyandrosta-1 4-Dien-3wne A solution of 17a-ethynyl-17}8-hydroxyandrost-4-en-3 one (0.5 g.), 2:3-dicyano-5:6-dichlorobenzoquinone (0.5 g.) and p-nitrophenol (0.05 g.) in purified dioxan (10 ml.) was heated under reflux for 12 /2 hours. The product was isolated as in Example 1 and crystallised from chloroform/ethanol to give 17a-ethynyl-17fl-hydroxyandrosta-l:4-dien-3-one as prisms, M.P. 225 to 228 C., [a] 13 (c. 0.7 in chloroform), A 244 mu, 10g e 4.2.

EXAMPLE 21 Pregna-I 4-Diene-3 :ZO-Dione Y A solution of progesterone (0.25 g.), 2:3-dicyanobenzoquinone (0.25 g.) and p-nitrophenol (0.05 g.) in dry benzene (5 ml.) was heated under reflux for 11 hours. The product was isolated as in Example 1 and crystallised from ether/hexane to give pregna-1:4-diene- 3:20-dione as prisms, M.P. 150 to 152 C., [a] +l26 (c. 0.45 in chloroform), A 244 my, log e 4.21.

EXAMPLE 22 16a-Methylpregna-1 :4-Diene-3 :20-Di0ne A solution of l6a-methylpregn-4-ene-3z20edione (0.5 g.) (Marker and Crooks, J. Amer. Chem. Soc., 1942, 64, 1280), 2:3-dicyano 5:6 dichlorobenzoquinone (0.5 g.)

and p-nitrophenol (0.05 g.) in dry benzene (10 ml.) was The product was heated under reflux for 9 /2 hours. isolated as in Example 1 and crystallised from ether/ petroleum ether (BR 60 to 80 C.) to give l6a-rnethylpregna-l:4-diene-3:20-dione as bIades MLP. 129 to 133 C., [oz] +l20.8 (c. 0.18 in chloroform), A 244 m log e 4.24.

EXAMPLE 23 Pregna-I :4: 16-Triene-3 :ZO-Diorze A solution of pregna 4:16 diene-3z20-dione (1 g.) (Butenandl and Schmidt-Theme, Ber., 1939, 72, 182), 2:3-dicyano-5:6-dichlorobenzoquinone (1 g.) and p-nitrophenol (0.1 g.) in dry benzene (20 ml.) was heated under reflux for 11 /2 hours. The product was isolated as in Example 1 and crystallised from dichlormethane/ methanol to give pregna-1:4: l6"-triene 3:20 dione as plates, M.P. 208 to 211 C., [a] (c. 0.46 in chloroform), A 240 mp, log e 4.31.

EXAMPLE 24 .17m Ethynyl-17B-Hydroxyandr0sta-1 :4 6-Trien-3one A solution of 17a-ethynyl-l7p-hydroxyandrosta-4;6- dien-3-one (1 g.) (prepared by treatment of 17a-ethynyl- 17,8-hydroxyandrost-4-en-3-one with chloranil in the manner well-known to those skilled in the art) and 2:3- dicyano-S:6-dichlorobenzoquinone (1 g.) in purified dioxan (15 ml.) was heated under reflux for 7 /2 hours. The product was isolated as in Example 1 and crystallized from dichloromethane/methanol to give l7u-ethynyl- 17B-hydroxyandrosta-l14:6-trien-3-one as prisms, M.P..

233 to 235 C., [oc] 104.2 (c. 1.0 in chloroform), A 255 my (log 6 3.93), 254 m (log @392) and 296 my. (log e 3.97).

7 EXAMPLE 25 21 -Acetxy-1 7a-Hydr0xypregna-1 :4 6 -Trien'e-- 3:11z20-Trione A solution of 21 acet'oxy 17a -'hydroxypregna-4:6-" diene-SzllzZO-trione (0.2 g.) (Mattox, Woroch, Fleisher and Kendall, J. Biol. Chem, 1952, 197, 261) and 2:3- dicyano-z6-dichlorobenzoquinone (0.2 g.) in purified dioxan (5 ml.) was heated under reflux for 22 /2 hours. The product Was isolated as in Example 1 and crystallised from acetone/hexane to give 21-acetoxy-17a-hydroxypregna-l:4:6-triene-3:11:20-trione as needles, M.P. 221 to 225 C., [eth l-280 (c. 0.4 in dioxan), A 223 mg (log 5. 4.02), 256 my (log e 3.97),an'd 298 mg (log 6 4.06).

EXAMPLE 26 9-Flu0r0-1I 8: 1 7,13-Dihydroxy-I 7a-Mezhylandr0sta- 1 4-Dien-3-one Ethyl 3-oxopregna-4:17(20')-dien-21-oate (250 mg.)- and 2:3-dich1oro-5-6-dicyanobenzoquinone (220 mg.) in dry benzene (4 ml.) were heated under reflux for 24 hours (Patel, Petrow, Royer and Stuart-Webb, J.C.S., 1-952, 161) and the product was isolated as in Example 1. Ethyl 3-oxopregna-1z4:17(20)-trien-21-oate crystallised from acetone/hexane (1:6) in prisms, M.P. 132 to 133" C., [a] +6l' (c. 0.29 in chloroform), k 228.5

m alog e 4.38 in ethanol v 1700, 1660, 1648, 1620 and 1 598-cm.- in Nujol.

EXAMPLE 28 20 ZO-Ethylenediaxypregna-l :4-Dien-3-0ne 20:20-ethylenedioxypregna-4-en-3-one (200 mg.) and 2:3-dichloro-5:6-dicyan0benzoquinone (180 mg.) in dry benzene (4 ml.) were heated under, reflux for 30 hours (Gut, J. Biol. Chem, 1956, 21, 1327 and the product was isolated as in' Example 1 20:20-ethylenedioxypregna- 1:4-dien-3-one' crystallised. from aqueous methanol; (80%) in flakes, M.P. 184 to 186 C.,, [a] +45 (c. 0.16 in chloroform), Amax, 244 my log e 4.15 in ethanol, vm 1665, 1625 and 1600 cm.- in Nujol.

EXAMPLE 29 17fl-Acet0xy-4-Methylaizdr osta l :4-Dien-3-0ize 4-methyltestosterone acetate (1 g.) (Sondheimer and Mazur, J. Amer. Chem. Soc, 1957, 79, 2906) and 2:3- dichloro-S:6-dicyanobenzoquinone (860 mg.) in dry benzene (12 ml.) were heated under reflux for 36 hours and the product isolated as in Example 1. 17fl-acetoxy-4- methylandrost-a-l :4-dien-3-one crystallised from methanol in prisms, M .P. 1.75 to 177 C., [a] +62 (.c. 0.24 in chloroform),f7t 245 melog 6 4.19 in ethanol.

7 EXAMPLE 30 Cholesta-I :4-diene-3:6-Di0ne A solution of cholest-4-ene-3:'6 dione (3 g.) Heilbronet a1., ILC.S.-, 1938, 102) and2:3'dicliloro-5:6-dicyanobenzoquinone (2 g.) in dry dioxan (201111.) washeated under reflux for- 1.4 hours. The product was isolated. as in Example 1 and crystallised from hexane to givechm [o:] +90.6 (c. 1.06 in chloroform), k 251 Ill/.0, log:

. (10 ml.) was heated under reflux for 10- hours. The

product was isolated as in Example 1 and crystallised from aqueous methanol to give li-hydroxypregna-lz4- dien-3-one as needles, M.P. 192 to 194 C., [a] +12 (c. 0.85 in chloroform), 1 244 111p. (log 6 4.16) and v 1665, 1620 and 1605 cmr EXAMPLE 32 Acetonide of 1 601:] 7a-Dihydroxypregna-1 :4-

Diene-sZO-Dione' A solution of thea'cetonide of 160:: 17a-dihydroxypregn- 4-ene-3z20-dione (1.3 g.) (Cooley et al., J.C.S., 1955,

4373), and 2:3-dichloro-5':6-dicyanobenzoquinone (1 g.) in dry dioxan (20 ml.) was heated under reflux for 14 hours. The product was isolated as in Example 1 and crystallised from acetone/hexane to give the acetonide of 16m:17a-dihydroxypregna-I:4-diene-3s20-dione' as rods, M.P. 197 to 199 C., [u] +83'.3'5 (c. 1.38 in chloro form), x 243.5 1111.0 log 6 4.14.

EXAMPLE 33 4-Chl0ro 17fi-Propionoxyandfosmd :4-Dien-3-o'ne A solution of 4-chloro-l7p-propionoxyandrost-4-en-3- one (0.55 g.) (Kirk, Patel and Petrow, J.C.S., 1956,; 1184) and 2:3-dichloro-5zfi-dicyanobenzoquinone (0.5 g.) in dry dioxan (5 ml.) was heated under reflux for 20 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give 4-chloro-17flpropionoxyandrosta-l:4-dien-3-one as needles, M.P. to 141 C., [a-] +75 (c.- 1.0 in chloroform), a 246 mp, log e 4.05.

EXAMPLE 34 1 7B-A cetoxy -2 -Methylana'rosta-l 4 -Dien-3-one A solution of 17B-acetoxy-2a-methylandrost-4-en 3-one. (1 g.) (Ringold and Rosenkrant'z, J. Org. Chem, 1956, 2 1-, (0.8 g.) in dry dioxan (10 ml.) was heated under reflux'. for 11 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give 175- acetoxy-Z-methylandtos'ta-1:4-dien-3-one as plates, M.P. to 167 C., [a] +48.1 (c. 1.12 in chloroform), Amax, 244.5 mg, log 6 4.17.

EXAMPLE 3S P'regna-I :4 :9 (1 1 -Tr'iene-3 :20-Dione A solution of pregna-4:9(1'1')'-diene-3:20-dione- (0.35 g.) (Shoppee and Reichstein, Helv. Chim. Acta, 1941, 24, 351') and 2:3-dichloro-5:6 dicyanobenzoquinone (0.3 g.)

in dry dioxan (5 ml.) was heated under reflux for 12 hours. The product was isolated as in Example 1 and crystallised from aqueous methanol to give pregna- 1:4:9(11)-triene 3:ZO-dione as small plates, M.P. 124 to 126 C., v 1700, 1660, 1620 and 1600 cm.-

We" claim:

1. A process comprising reacting a steroid compound selected from the group consisting of 3-oxo-A and 3-' o'xo-M- derivatives of steroid compounds of the androstane, pregn'ane, stigmastane, cholestane and spirost'ane series with a compound selected from the group consisting of 2:3-dicyano-1:4-benzoquinone, and chlorine-substituted 2:3dicyano-1:4-benzoquinone having up to two chlorine atoms, in an organic solvent, to thereby pro-' vide the-corresponding l-dehydro compound.-

2. A process as claimed in claim 1 wherein 2:3-cli- 1333-) and 2: 3-dichloro-5 6-dicyanobenzoquinone 9 cyano-z6-dichloro-1:4-benzoquinone is reacted with said steroid starting material.

3. A process as claimed in claim 1 wherein said solvent is selected from the groups consisting of benzene and dioxan.

4. A process as claimed in claim 1 wherein the reaction is carried out at a temperature between 80 C. and 110 C.

5. A process as claimed in claim 1 wherein the reaction is carried out in the presence of a catalytic quantity of p-nitrophenol.

6. The process of claim 1 wherein the first two rings of the steroid nucleus of the steroid starting material have the following structure:

7. The process of claim 1 wherein the first two rings of the steroid nucleus of the steroid starting material have the following structure:

8. The process of claim 1 wherein the starting material is 17a-hydroxyprogesterone.

9. The process of claim 1 wherein the starting material is cortisone acetate.

10. The process of claim 1 wherein the starting material is 11u-hydroxypregn-4-ene-3:20-dione.

11. The process of claim 1 wherein the starting material is 90c fiuoro 11,3:l7fl-dihydroxy-17a-methylandrosta-4-ene-3-one.

12. The process of claim 1 wherein the starting material is the acetonide of 16a:l7u-dihydroxypregn-4-ene- 3:20-dione.

References Cited in the file of this patent UNITED STATES PATENTS 2,705,719 Rubin Apr. 5, 1955 2,793,208 Korman et al. May 21, 1957 2,837,464 Nobile June 3, 1958 2,877,239 Agnello et al. Mar. 10, 1959 2,880,217 Thoma et al. Mar. 31, 1959 2,882,282 Agnello et a1 Apr. 14, 1959 2,883,379 Moreland et a1 Apr. 21, 1959 2,899,447 Gould et al Aug. 11, 1959 OTHER REFERENCES Cooley et al.: J.C.S., vol. (1955), pp. 4373-76. 

1. A PROCESS COMPRISING REACTING A STEROID COMPOUND SELECTED FROM THE GROUP CONSISTING OF 3-OXO-$4 AND 3OXO-$4.6 DERIVATIVES OF STEROID COMPOUNDS OF THE ANDROS TANE, PREGNANE, STIGMASTANE, CHOLESTANE AND SPIROSTANE SERIES WITH A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 2:3-DICANO-1:4-BENZOQUINONE, AND CHLOEINE-SUBSTITUTED 2:3-DICYANO-1:4-BENZOQUINONE HAVING UP TO TWO CHLORINE ATOMS, IN AN ORGANIC SOLVENT, TO THEREBY PROVIDE THE CORRESPONDING 1-DEHYDRO COMPOUND. 